The overall objectives of this proposal are three-fold: 1) to determine the mechanism(s) by which activated macrophages induce an aberrant cycle of reductive division in tumor cells and the relationship of this cycle of reductive division to tumor cell death, 2) to establish several tumor cell lines resistant to macrophage mediated killing as a tool for evaluating the role of macrophage mediated events in tumor growth, 3) to use monoclonal antibodies to macrophages and antisera to Ia antigens to characterize the interrelationships between the biochemical events an the membrane antigens associated with macrophage maturation and/or differentiation. Experiments will involve determsining the mechanism(s) by which activated macrophages in vitro induce an amtotic cycle of reductive division in tumor cells. We will determine the relationship of 5-FU mediated reductive division in Ehrlich ascites tumor cells in vivo to macrophage activation to establish whether or not a common mechanism via macrophage mediation exists both in the in vivo 5-FU induced and in vitro macrophage induced reductive division. Ascites and solid tumor models will be used to determine if agents such as C. parvum and pyran, which induce macrophage activation in vivo, can also induce reductive division of tumor cells in vivo. The relationship between activated macrophage tumor cell cytotoxicity and the ploidy (DNA content) of the target cell will be established. Lastly, in this area, attempts will be made to establish a series of mutant cell lines resistant to macrophage mediated cytotoxicty and to establish in vivo and in vitro the characxteristics of these cell lines. Monoclonal hybridoma antibodies to macrophage surface antigens will be used to identify surface antigens associated with the different populations of mouse macrophages. The surface antigens will be characterized by polyacrylamide gel electrophoresis and the relationship of a given surface antigen to macrophage function analyzed. Antisera to different macrophage subpopulations and to Ia antigens will then be used to determine which subpopulation of macrophages are the precursors and ultimate effectors with respect to tumor cell cytotoxicity.